2002ISHLT

LUNG TRANSPLANTATION

Overall

2002ISHLT

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

0

200

400

600

800

1000

1200

1400

1600

1800

Nu

mb

er

of

Tra

ns

pla

nts

19

85

19

86

19

87

19

88

19

89

19

90

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

*

Bilateral/Double LungSingle Lung

13 15 47 80185

408

686

902

10691204

1341133714161413140815081554

* Numbers may be low due to delayed reporting.

2002ISHLT

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND LOCATION

0

200

400

600

800

1000

1200

1400

1600

Nu

mb

er

of

Tra

ns

pla

nts

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

*

* Numbers may be low due to delayed reporting.

2002ISHLT

LUNG TRANSPLANTS: Donor Age by Year of Transplant

0%

20%

40%

60%

80%

100%

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

*

Year of Transplant

% o

f T

ran

spla

nts

0-10 11-17 18-34 35-49 50-59 60+

2002ISHLT

AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1985-2001)

0

10

20

30

40

50

% o

f tr

ansp

lan

ts

<1 1-5 6-10 11-17 18-34 35-49 50-64 65+

Recipient Age

2002ISHLT

AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS BY ERA

0

10

20

30

40

50

<1 1-5

6-10

11-1

7

18-3

4

35-4

9

50-6

465

+ <1 1-5

6-10

11-1

7

18-3

4

35-4

9

50-6

465

+

% o

f tr

ansp

lan

ts

1985-1996 1997-2001

2002ISHLT

LUNG TRANSPLANTATIONActuarial Survival (1990-2000)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11

Years Post Transplantation

Sur

viva

l (%

)

Bilateral/Double Lung (N=6,448)

Single Lung (N=7,798)

All Lungs (N=14,246)

Double lung: 1/2-life = 4.9 Years; Conditional 1/2-life = 7.9 YearsSingle lung: 1/2-life = 3.7 Years; Conditional 1/2-life = 5.9 YearsAll lungs: 1/2-life = 4.1 Years; Conditional 1/2-life = 6.5 Years

2002ISHLT

LUNG TRANSPLANTATION

Adult Recipients

2002ISHLT

ADULT LUNG TRANSPLANTATION: Indications (1995-2001)

DIAGNOSIS SLT (N = 4,663) BLT (N = 4,118) TOTAL (N = 8,781)

COPD/Emphysema 2,536 54.4% 926 22.5% 3,462 39.4%

IPF 1,110 23.8% 376 9.1% 1,486 16.9%

CF 52 1.1% 1,360 33.0% 1,412 16.1%

Alpha-1 408 8.7% 407 9.9% 815 9.3%

PPH 61 1.3% 340 8.3% 401 4.6%

Sarcoidosis 126 2.7% 106 2.6% 232 2.6%

Bronchiectasis 14 0.3% 176 4.3% 190 2.2%

Congenital Heart Disease 8 0.2% 95 2.3% 103 1.2%

LAM 42 0.9% 53 1.3% 95 1.1%

Re-TX: OB 44 0.9% 43 1.0% 87 1.0%

OB (Non-ReTX) 32 0.7% 50 1.2% 82 0.9%

Re-TX: Non-OB 33 0.7% 36 0.9% 69 0.8%

Connective Tissue Disorder

20 0.4% 18 0.4% 38 0.4%

Cancer 7 0.2% 28 0.7% 35 0.4%

Histiocytosis X 11 0.2% 8 0.2% 19 0.2%

Other 159 3.4% 96 2.3% 255 2.9%

2002ISHLT

ADULT LUNG TRANSPLANTATION: Indications (1995-2001)

54%

24%

9%

1%

3%

1%2%

6%

22%

34%2%

9%

10%

8%

2%

1%4%

1%

4%

3%

COPD/Emphysema CF Congenital Heart DiseaseBronchiectasis Re-TX IPFAlpha-1 PPH SarcoidosisOB (Non-ReTX) LAM Other

Single Lung Transplants

Bilateral/Double Lung Transplants

2002ISHLT

ADULT LUNG TRANSPLANTATIONIndications By Year

0

20

40

60

80

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Transplant Year

% o

f T

ran

sp

lan

ts

Cystic Fibrosis IPF Emphysema PPH

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival by Era (1988-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7 8

Years Post-Transplantation

Su

rviv

al (

%)

1988-1992 (N=2,093)1993-1997 (N=5,999)1998-2001 (N=5,595)

Survival comparisons by era1988-1992 vs. 1993-1997: p = 0.0071988-1992 vs. 1998-2001: p < 0.00011993-1997 vs. 1998-2001: p = 0.003

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival by Age Group (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7 8

Years Post-Transplantation

Sur

viva

l (%

)

18-34 (N=2,451)35-49 (N=4,114)50-64 (N=6,377)65+ (N=347)

Survival comparisons by age group18-34 vs. 50-64: p < 0.000118-34 vs. 65+: p = 0.000935-49 vs. 50-64: p < 0.000135-49 vs. 65+: p = 0.0004

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival By Diagnosis (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years Post-Transplantation

Sur

viva

l (%

)

Alpha-1 Antitrypsin (N=1,288) Cystic Fibrosis (N=1,809)Emphysema/COPD (N=4,643) IPF (N=1,981)PPH (N=714) Sarcoidosis (N = 303)

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival By Procedure Type

Diagnosis: Alpha-1 Antitrypsin Deficiency (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N = 739)

Double Lung (N=549) P = 0.03

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival by Procedure Type

Diagnosis: Emphysema/COPD (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N =3,513)

Double Lung (N=1,130)P < 0.0001

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival by Procedure Type

Diagnosis: IPF (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N =1,547)

Double Lung (N=434)P = 0.2

2002ISHLT

ADULT LUNG TRANSPLANTATIONActuarial Survival by Procedure Type

Diagnosis: PPH (1990-2001)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N =250)

Double Lung (N=464)P = 0.4

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

In Descending Order of Magnitude

N=5,242

VARIABLE Odds Ratio P-value

95% Confidence

Interval

Diagnosis: Congenital Heart Disease 2.07 0.007 1.22 -3.50

Previous Transplant 2.02 0.0003 1.38 -2.97

Ventilator 1.77 0.03 1.05 -2.98

Total Assistance for ADL 1.52 0.002 1.17 -1.97

In ICU or Hospital 1.48 0.01 1.09 -2.01

Diagnosis: PPH 1.47 0.01 1.08 -2.02

Double Lung TX/Diagnosis: IPF 1.38 0.04 1.01 -1.88

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

In Descending Order of Magnitude

N=5,242

VARIABLE Odds Ratio P-value

95% Confidence

Interval

Donor CMV+/Recipient CMV- 1.37 0.0007 1.14 -1.65

Donor COD: Other (not head trauma, CVA, CNS tumor, or anoxia) 1.30 0.02 1.04 -1.62

Year of Transplant: 1996 1.26 0.005 1.07 -1.47

Donor Cigarette History 1.21 0.02 1.03 -1.41

Donor/Recipient Gender Mismatch 1.19 0.02 1.03 -1.37

Diagnosis: COPD 0.55 <.0001 0.47 -0.65

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

Continuous Factors

N=5,242

VARIABLE Odds Ratio p-value Recipient Age – linear < 0.0001

20 years 0.52

35 years 0.75

50 years 1.08

65 years 1.55

Donor Age - quadratic 0.001

20 years 1.06

35 years 1.01

50 years 1.21

65 years 1.83

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

Continuous Factors

N=5,242

VARIABLE Odds Ratio p-value Recipient BMI – linear 0.004

20 0.91

25 1.06

30 1.23

35 1.43

Center Volume - linear < 0.0001 5 transplants/year 1.21

10 transplants/year 1.14 30 transplants/year 0.92 60 transplants/year 0.67

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

Continuous Factors

N=5,242

VARIABLE Odds Ratio p-value Bilirubin (mg/dl) – linear 0.03

1 0.99 5 1.10

10 1.25 25 1.87 50 3.63

2002ISHLT

ADULT LUNG TRANSPLANTS (1996-2001) Factors Not Significant for 1 Year Mortality

•Steroid dependency•Ischemia time•% Predicted FeV1•% Predicted FVC•Transfusions•Diabetes•Weight (donor)•Height (donor)•Donor clinical infection•Donor history of hypertension•Donor given steroids

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality

In Descending Order of Magnitude

N=3,098

VARIABLE Odds Ratio P-value

95% Confidence

Interval

Diagnosis: Congenital Heart Disease 3.04 0.0007 1.60 -5.77

In ICU 2.70 0.001 1.48 -4.93

Previous Transplant 2.26 0.0007 1.41 -3.63

Double Lung TX/Diagnosis: IPF 1.73 0.009 1.15 -2.62

Donor CMV+/Recipient CMV- 1.48 0.0009 1.18 -1.87

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality

In Descending Order of Magnitude

N=3,098

VARIABLE Odds Ratio P-value

95% Confidence

Interval

Donor COD: Other (not head trauma, CVA, CNS tumor, or anoxia) 1.42 0.004 1.12 -1.81

Donor Cigarette History 1.21 0.046 1.00 -1.45

Female Recipient 0.74 0.002 0.61 -0.90

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality

Continuous Factors

N=3,098

VARIABLE Odds Ratio p-value Recipient Age - linear <0.0001

Recipient Age – quadratic 0.0001 20 years 1.22 35 years 0.91 50 years 1.08 65 years 2.01

Donor Age - quadratic < 0.0001

20 years 1.12 35 years 1.02 50 years 1.42 65 years 3.06

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality

Continuous Factors

N=3,098

VARIABLE Odds Ratio p-value Recipient BMI – linear 0.004

20 0.80

25 1.15

30 1.64

35 2.34

Center Volume - linear 0.0001

5 transplants/year 1.21

10 transplants/year 1.15

30 transplants/year 0.92

60 transplants/year 0.66

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality

Continuous Factors

N=3,098

VARIABLE Odds Ratio p-value Recipient Weight – linear 0.04

40 kg 1.49

60 kg 1.10

80 kg 0.82

100 kg 0.61

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Factors Not Significant for 5 Year Mortality

•Steroid dependency•Ventilator•Ischemia time•% Predicted FeV1•% Predicted FVC•Transfusions•Diabetes•Weight (donor)•Height (donor)•Donor clinical infection•Donor history of hypertension•Donor given steroids

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year

In Descending Order of Magnitude

N=2,285

VARIABLE Odds Ratio P-value

95% Confidence

Interval Bronchiolitis Obliterans during 1st Year

3.67 <.0001 2.57 -5.24

Donor CMV+/Recipient CMV- 1.36 0.02 1.04 -1.79

Rejection during 1st Year 1.30 0.005 1.08 -1.56

Double Lung Transplant 0.77 0.01 0.62 -0.95

2002ISHLT

ADULT LUNG TRANSPLANTS (April 1994-December 1996)

Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year

Continuous Factors

N=2,285

VARIABLE Odds Ratio p-value Recipient Age – linear <.0001

Recipient Age – quadratic <.0001

20 years 1.34

35 years 0.93

50 years 1.08

65 years 2.08

Donor Age - quadratic 0.004

20 years 1.10

35 years 1.01

50 years 1.33

65 years 2.49

2002ISHLT

ADULT LUNG RECIPIENTSFunctional Status (April 1994 – December 2001)

0%

20%

40%

60%

80%

100%

1 Year (N=5,039) 3 Years (N=3,516) 5 Years (N=1,372)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

2002ISHLT

ADULT LUNG RECIPIENTSEmployment Status (U.S.: April 1994 – December 2001)

0%

20%

40%

60%

80%

100%

1 Year (N = 3,738)

3 Years (N=2,229)

5 Years (N = 1,194)

Retired

Not Working

Working Part Time

Working Full Time

2002ISHLT

ADULT LUNG RECIPIENTS: Rehospitalization Post-transplant (April 1994 - December 2001)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 4,703)

Between 2 and 3 Years (N = 2,811)

Between 4 and 5 Years (N = 1,541)

No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Only Hospitalized, Infection OnlyHospitalized, Rejection and Infection

2002ISHLT

0

5

10

15

20

25

30

35

40

45

Any Induction (N = 911)

Polyclonal ATG/ALG (N = 456)

OKT3 (N = 94) IL2-R Antagonist (N = 426)

% o

f p

ati

en

tsADULT LUNG RECIPIENTS

Induction Immunosuppression For follow-ups between October 1999 and December 2001

2002ISHLT

0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 1,417)

Year 5 (N = 625)

ADULT LUNG RECIPIENTS Maintenance Immunosuppression At Any Time During Follow-up Period

For follow-ups between October 1999 and December 2001

2002ISHLT

0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 1,177) Year 5 (N = 547)

ADULT LUNG RECIPIENTSMaintenance Immunosuppression At Time of Follow-up

For follow-ups between October 1999 and December 2001

2002ISHLT

0

20

40

60

80

100

CalcineurinInhibitor

CellCycle Prednisone CalcineurinInhibitor

CellCycle Prednisone

% o

f P

ati

en

ts

CyA

TacTac

CyA

AZA

AZA

MMF

MMF

ADULT LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

For follow-ups between October 1999 and December 2001

1 Year Follow-up (N = 1,177) 5 Year Follow-up (N = 547)

2002ISHLT

0%

20%

40%

60%

80%

100%

Year 1 (N = 1,177) Year 5 (N = 547)

% o

f P

atie

nts

None Given

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

ADULT LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

For follow-ups between October 1999 and December 2001

2002ISHLT

POST-LUNG TRANSPLANT MORBIDITYFor Adult Recipients (April 1994-December 2001)

Outcome By 1 Year By 5 Years

Hypertension 49.5% (N=4,580) 87.1% (N=761)

Renal Function (N=4,557) (N=792) Normal 76.1% 61.2% Renal Dysfunction 14.1% 20.8% Creatinine>2.5 mg/dl 8.2% 14.1% Chronic Dialysis 1.6% 2.9% Renal Transplant 0.0% 0.9%

Hyperlipidemia 14.8% (N=4,760) 41.7% (N=823)

Diabetes 17.5% (N=4,535) 25.9% (N=738)

Bronchiolitis Obliterans 9.8% (N=4,237 37.2% (N=562)

2002ISHLT

Freedom from Bronchiolitis Obliterans For Adult Lung Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

ree

from

CA

V

2002ISHLT

Freedom from Renal Dysfunction*For Adult Lung Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

reed

om fr

om R

enal

D

ysfu

nctio

n

* Renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant

2002ISHLT

MALIGNANCY POST-LUNG TRANSPLANTATION FOR ADULTSCumulative Incidence for Survivors (April 1994-December 2001)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 4,583 (96.0%) 731 (87.2%)

Malignancy (all types combined) 189 (4.0%) 107 (12.8%)

Malignancy Type

Skin 37 54

Lymph 91 15

Other 39 21

Lymph + Skin 3

Lymph + Other 4

Skin + Other 2

Type Not Reported 22 8

2002ISHLT

Freedom from MalignancyFor Adult Lung Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

ree

fro

m M

alig

nan

cy

All malignancy Lymph Skin Other

2002ISHLT

ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (1982-2001)

0-30 Days

(N = 962)

31 Days - 1 Year

(N = 1,230)

>1 Year - 3 Years

(N = 953)>3 Year - 5 Years

(N = 479)

CAD 12 1.2% 10 0.8% 11 1.2% 7 1.5%

Cardiac 89 9.3% 44 3.5% 20 2.1% 15 3.1%

Malignancy, Other 0 0.0% 24 1.9% 39 4.1% 38 7.9%

Lymphoma 1 0.1% 40 3.2% 23 2.4% 8 1.7%

CMV 5 0.5% 51 4.0% 16 1.7% 3 0.6%

Acute Rejection 57 5.9% 55 4.4% 20 2.1% 4 0.8%

Infection, Non-CMV 237 24.6% 484 38.3% 237 24.9% 90 18.8%

Bronchiolitis 7 0.7% 75 5.9% 286 30.0% 158 33.0%

Primary Graft Failure 158 16.4% 75 5.9% 55 5.8% 19 4.0%

Graft Failure - Other 141 14.7% 140 11.1% 97 10.2% 66 13.8%

Technical 85 8.8% 38 3.0% 9 0.9% 1 0.2%

Other 170 17.7% 227 18.0% 140 14.7% 70 14.6%

Total 962 100.0% 1263 100.0% 953 100.0% 479 100.0%

2002ISHLT

ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (1982-2001)

0%

20%

40%

60%

80%

100%

0-30 Days (N = 962)

31 Days - 1 Year (N = 1,230)

>1 Year - 3 Years(N = 953)

>3 Years - 5Years (N =

479)

> 5 Years (N = 301)

Pe

rce

nta

ge

of

De

ath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Timing of Death

2002ISHLT

ADULT LUNG TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in 0-30 Days

0%

20%

40%

60%

80%

100%

1987-1991 (N = 157) 1992-1996 (N = 493) 1997-2001 (N = 311)

Per

cent

age

of d

eath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Year of Transplant

2002ISHLT

ADULT LUNG TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in 31 Days – 1 Year

0%

20%

40%

60%

80%

100%

1987-1991 (N = 149) 1992-1996 (N = 663) 1997-2001 (N = 417)

Per

cent

age

of d

eath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Year of Transplant

2002ISHLT

ADULT LUNG TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >1 Year – 3 Years

0%

20%

40%

60%

80%

100%

1987-1991 (N = 123) 1992-1996 (N = 598) 1997-2001 (N = 232)

Per

cent

age

of d

eath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Year of Transplant

2002ISHLT

ADULT LUNG TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >3 Years – 5 Years

0%

20%

40%

60%

80%

100%

1987-1991 (N = 102) 1992-1996 (N = 353) 1997-2001 (N = 24)

Pe

rce

nta

ge

of

de

ath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Year of Transplant

2002ISHLT

ADULT LUNG TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >5 Years

0%

20%

40%

60%

80%

100%

1992-1996 (N = 110) 1997-2001 (N = 188)

Pe

rce

nta

ge

of

de

ath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Bronchiolitis

Infection, Non-CMV

Acute Rejection

CMV

Lymphoma

Malignancy, Other

Cardiac

CAD

Year of Transplant